N.sup.4 -acyl-5'-deoxy-5-fluorocytidine derivatives of the formula set forth below are compounds having antitumor activity [Japanese Journal of Cancer Research, Vol. 81, pp. 188-195. (1990)]: ##STR1## wherein R.sup.2 is alkyl, cycloalkyl, alkenyl, aralkyl, aryl or alkoxy.
A process for producing said compounds starting from 5'-deoxy-5-flurocytidine is described in Japanese Patent Application Kokai No. 153,696/1989.
In order to selectively introduce acyl (R.sup.2 CO) into an amino radical of this compound, a protective radical such as an isopropylidene radical, a silyl radical or the like is first introduced into a hydroxy radical in the sugar part of this compound, subsequently acylating an amino radical in the cytosine-base part and finally eliminating the protective radical using an acid catalyst or the like. ##STR2## wherein R.sup.2 is as above.
That is, the above production method comprises (1) introduction of a protective radical into a hydroxy radical of 5'-deoxy-5-fluorocyctidine, (2) acylation of an amino radical and (3) elimination of said protective radical. In said steps, a protective radical which is an unnecessary radical In the molecular structure of the final compound, must be introduced and eliminated.
In addition, 5'-deoxy-5-fluorocytidine as a starting substance is produced, for example, from 5-fluorocytosine through 5-fluorocytidine [Chem. Pharm. Bull., Vol. 26, No. 10, p. 2,990 (1978)]. However, this method requires many steps (cf., Japanese Patent Publication No. 34,479/1983). ##STR3##
Anyway, the conventional production methods of N.sup.4 -acyl-5'-deoxy-5-flurocytidine derivatives involve steps in which protection of an hydroxy radical in the sugar part and/or an amino radical in the cytosine part with a suitable protective radical(s) and elimination of said protective radical(s) after completion of the desired reactions. These steps must be carried out repeatedly so that it is difficult to say they are easily performable methods on an industrial scale.
A process for deacylation of N.sup.4,0-acylcytidine derivatives has been described [J. H. vanBoom et al, Nucleic Acids Research, Vol. 4 (4), pp. 1,047-1,063 (1977)]. Generally, it is known that 0-acyl is eliminated mainly when N.sup.4,0-acylcytidine derivatives react with an alkali. However, the cutting of N-acyl also takes place, so that complicated operations of separation and purification are required in order to obtain a compound from which 0-acyl alone has been eliminated at satisfactory purity.
An N.sup.4 -acyl radical of N.sup.4,0-acylcytidine derivative is relatively easily cut. In case, for example, of N.sup.4,2'-0,3'-0,5'-0-tetracylcytidine derivative, it is known that N-acyl alone can be eliminated selectively only by merely heating the said derivative in alcohol (cf. Japanese Patent Application Kokai No. 23,085/1977).
In addition, it is also known that, when a 5-fluoro-N.sup.4, 2'-0,3'-0,5'-0-tetracylcytidine derivative is treated with 0.5N-sodium methoxide in methanol at room temperature, all acyl radicals are eliminated to produce 5-fluorocytidine [Chem. Pharm. Bull., Vol. 26, No. 10, p. 2,990 (1978)].